Strain improvement of industrial microorganisms is required at both the clinical testing stage and commercialization stage of drug development. Although strain improvement plays an enormous economic role in reducing the costs of pharmaceutical manufacturing, this role is generally unrecognized by the public, except during a national crisis when demand for a drug may soar. The first such crisis involved the production of penicillin during World War II. Future crises may involve drugs needed to counter bio-terrorist attacks. Unfortunately, the empirical genetic methods used for strain improvement have not substantially improved since the 1940's. Modern genetic engineering technology offers hope that newer rational methods can be developed, but more basic research is required. This research is no longer being rigorously pursued by the pharmaceutical industry. In Phase I of this project we significantly broadened our understanding of the genetics of erythromycin production by cloning and sequencing a new erythromycin gene cluster. In Phase II we are proposing to apply this new basic knowledge to the development of modern methods of strain improvement for erythromycin and other important drugs.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
2R44GM063278-02A1
Application #
6741679
Study Section
Special Emphasis Panel (ZRG1-SSS-K (10))
Program Officer
Jones, Warren
Project Start
2001-07-16
Project End
2006-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
2
Fiscal Year
2004
Total Cost
$430,489
Indirect Cost
Name
Fermalogic, Inc.
Department
Type
DUNS #
798525234
City
Chicago
State
IL
Country
United States
Zip Code
60610
Reeves, Andrew R; Weber, J Mark (2012) Metabolic engineering of antibiotic-producing actinomycetes using in vitro transposon mutagenesis. Methods Mol Biol 834:153-75
Reeves, Andrew R; Brikun, Igor A; Cernota, William H et al. (2007) Engineering of the methylmalonyl-CoA metabolite node of Saccharopolyspora erythraea for increased erythromycin production. Metab Eng 9:293-303
Reeves, Andrew R; Brikun, Igor A; Cernota, William H et al. (2006) Effects of methylmalonyl-CoA mutase gene knockouts on erythromycin production in carbohydrate-based and oil-based fermentations of Saccharopolyspora erythraea. J Ind Microbiol Biotechnol 33:600-9